Cardiotocography measures the human fetal heart rate and uterine activity using ultrasound. While it has been a mainstay in antepartum care since the 1960s, cardiotocograms consist of complex signals that have proven difficult for clinicians to interpret accurately and as such clinical inference is often difficult and unreliable. Previous attempts at codifying approaches to analyzing the features within these signals have failed to demonstrate reliability or gain sufficient traction. Since the early 1990s, the Dawes-Redman system of automated computer analysis of cardiotocography signals has enabled robust analysis of cardiotocographic signal features, employing empirically-derived criteria for assessing fetal wellbeing in the antepartum. Over the past 30 years, the Dawes-Redman system has been iteratively updated, now incorporating analyses from over 100,000 pregnancies. In this review, we examine the history of cardiotocography, signal processing methodologies and feature identification, the development of the Dawes-Redman system, and its clinical applications.

Cardiotocography measures the human fetal heart rate and uterine activity using ultrasound. While it has been a mainstay in antepartum care since the 1960s, cardiotocograms consist of complex signals that have proven difficult for clinicians to interpret accurately and as such clinical inference is often difficult and unreliable. Previous attempts at codifying approaches to analyzing the features within these signals have failed to demonstrate reliability or gain sufficient traction. Since the early 1990s, the Dawes-Redman system of automated computer analysis of cardiotocography signals has enabled robust analysis of cardiotocographic signal features, employing empirically-derived criteria for assessing fetal wellbeing in the antepartum. Over the past 30 years, the Dawes-Redman system has been iteratively updated, now incorporating analyses from over 100,000 pregnancies. In this review, we examine the history of cardiotocography, signal processing methodologies and feature identification, the development of the Dawes-Redman system, and its clinical applications.

The syncytiotrophoblast, a fused single-cell layer between mother and fetus, constitutively releases extracellular vesicles (STBEV) directly into the maternal circulation. STBEV contain a variety of proteins and RNA which can be targeted to specific cells. In preeclampsia, asymptomatic placental oxidative stress is a precursor to later multi-organ dysfunction in the mother. Increased STBEV release in preeclampsia is considered a manifestation of syncytiotrophoblast stress, which may play a key role in signaling between fetus and mother. STBEV release in preeclampsia changes, both in terms of volume and content. In this review, we outline the latest advances in STBEV isolation and detection. We consider evidence for differential STBEV release, protein cargo and RNA content in preeclampsia, highlighting common pitfalls in study design. We summarise studies to date demonstrating STBEV actions on target cells. Ultimately, we consider how STBEV fit into the pathophysiology of the heterogeneous syndrome of preeclampsia. The key unifying concept in early- and late-onset preeclampsia is syncytiotrophoblast stress. We submit that STBEV are the key stress signal in preeclampsia. We believe that further investigation of STBEV release, content, and actions may offer valuable insights into preeclampsia pathophysiology and potential new clinical diagnostics and therapeutic targets.

The syncytiotrophoblast, a fused single-cell layer between mother and fetus, constitutively releases extracellular vesicles (STBEV) directly into the maternal circulation. STBEV contain a variety of proteins and RNA which can be targeted to specific cells. In preeclampsia, asymptomatic placental oxidative stress is a precursor to later multi-organ dysfunction in the mother. Increased STBEV release in preeclampsia is considered a manifestation of syncytiotrophoblast stress, which may play a key role in signaling between fetus and mother. STBEV release in preeclampsia changes, both in terms of volume and content. In this review, we outline the latest advances in STBEV isolation and detection. We consider evidence for differential STBEV release, protein cargo and RNA content in preeclampsia, highlighting common pitfalls in study design. We summarise studies to date demonstrating STBEV actions on target cells. Ultimately, we consider how STBEV fit into the pathophysiology of the heterogeneous syndrome of preeclampsia. The key unifying concept in early- and late-onset preeclampsia is syncytiotrophoblast stress. We submit that STBEV are the key stress signal in preeclampsia. We believe that further investigation of STBEV release, content, and actions may offer valuable insights into preeclampsia pathophysiology and potential new clinical diagnostics and therapeutic targets.

OBJECTIVE: Although previous research has suggested that risk for reoperation among hysteroscopic sterilization (HS) patients is more than ten times higher than for patients undergoing standard laparoscopic tubal ligation, little has been reported about these subsequent procedures. METHODS: This descriptive cohort study used a confidential online questionnaire to gather data from women (n=3,803) who volunteered information on HS followed by device removal surgery performed due to new symptoms developing after Essure placement. RESULTS: In this sample, mean age was 35.6 years and women undergoing hysterectomy after HS comprised 64.9% (n=2,468). Median interval between HS and hysterectomy was 3.7 (interquartile range, 3.9) years and mean age at hysterectomy was 36.3 years. Some patients (n=1,035) sought removal of HS devices and fallopian tubes only, while other miscellaneous gynecological procedures were also occasionally performed for Essure-associated symptoms. When data from all patients who had any post-Essure surgery besides hysterectomy were aggregated (e.g., device removal +“other” cases, n=1,335) and compared to those cases undergoing hysterectomy, mean age was significantly lower than for the hysterectomy group (34.4 vs. 36.3 years, respectively; P<0.01); uterus-conserving surgeries were also typically performed significantly earlier than hysterectomy (P<0.01). CONCLUSION: This investigation is the first to characterize specific gynecological operations after Essure, and suggests that the predominant surgical answer to HS complaints is hysterectomy for many women. Dissatisfaction with HS may represent an important indication for hysterectomy and additional study is needed to quantify this phenomenon.
Cohort Studies ; Contraception ; Device Removal ; Fallopian Tubes ; Female ; Humans ; Hysterectomy ; Reoperation ; Sterilization* ; Sterilization, Tubal

Essure (Bayer) received approval from the U.S. Food and Drugs Administration as a permanent non-hormonal contraceptive implant in November 2002. While the use of Essure in the management of hydrosalpinx prior to in vitro fertilization (IVF) remains off-label, it has been used specifically for this purpose since at least 2007. Although most published reports on Essure placement before IVF have been reassuring, clinical experience remains limited, and no randomized studies have demonstrated the safety or efficacy of Essure in this context. In fact, no published guidelines deal with patient selection or counseling regarding the Essure procedure specifically in the context of IVF. Although Essure is an irreversible birth control option, some patients request the surgical removal of the implants for various reasons. While these patients could eventually undergo hysterectomy, at present no standardized technique exists for simple Essure removal with conservation of the uterus. This article emphasizes new aspects of the Essure procedure, as we describe the first known association between the placement of Essure implants and the subsequent development of fluid within the uterine cavity, which resolved after the surgical removal of both devices.
Contraception ; Counseling* ; Fertilization in Vitro* ; Humans ; Hysterectomy ; Laparoscopy ; Patient Selection ; Uterus

OBJECTIVE: This investigation examined data on unplanned pregnancies following hysteroscopic sterilization (HS). METHODS: A confidential questionnaire was used to collect data from women with medically confirmed pregnancy (n=103) registered after undergoing HS. RESULTS: Mean (+/-SD) patient age and body mass index (BMI) were 29.5+/-4.6 years and 27.7+/-6.1 kg/m2, respectively. Peak pregnancy incidence was reported at 10 months after HS, although <3% of unplanned pregnancies occurred within the first three months following HS. Mean (+/-SD) interval between HS and pregnancy was 19.6+/-14.9 (range, 2 to 84) months. Patients age > or =30 years and BMI <25 reported conception after HS somewhat sooner than younger patients, although the differences in time to pregnancy were not significant (P=0.24 and 0.09, respectively). The recommended post-HS hysterosalpingogram (to confirm proper placement and bilateral tubal occlusion) was obtained by 66% (68/103) of respondents. CONCLUSION: This report is the first to provide patient-derived data on contraceptive failures after HS. While adherence to backup contraception 3 months after HS can be poor, many unintended pregnancies with HS occur long after the interval when alternate contraceptive is required. Many patients who obtain HS appear to ignore the manufacturer's guidance regarding the post-procedure hysterosalpingogram to confirm proper device placement, although limited insurance coverage likely contributes to this problem. The greatest number of unplanned pregnancies occurred 10 months after HS, but some unplanned pregnancies were reported up to 7 years later. Age, BMI, or surgical history are unlikely to predict contraceptive failure with HS. Further follow-up studies are planned to capture additional data on this issue.
Body Mass Index ; Contraception ; Surveys and Questionnaires ; Female ; Fertilization ; Follow-Up Studies ; Humans ; Incidence ; Insurance Coverage ; Pregnancy ; Pregnancy, Unplanned* ; Sterilization* ; Time-to-Pregnancy

OBJECTIVEDiagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheezing. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents. The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms.

METHODSInfants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB.

RESULTSNineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported.

CONCLUSIONSIn infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.

Bethanechol ; therapeutic use ; Cough ; drug therapy ; Double-Blind Method ; Female ; Gastroesophageal Reflux ; complications ; Humans ; Hydrogen-Ion Concentration ; Infant ; Male ; Omeprazole ; therapeutic use ; Pilot Projects ; Respiratory Sounds ; etiology

We evaluated a biodegradable graft for reconstruction of rat vasa deferentia with long obstructed or missing segments. A total of 47 Sprague-Dawley rats underwent bilateral vasectomy and were divided into groups according to length of the vas deferens affected (0.5, 1, 1.5 cm). After 8 weeks, poly-(D,L-lactide) (PDLA) grafts were used to reconnect the vas deferens. Grafts and adjoining vasa deferentia were excised 8 and 12 weeks later and evaluated microscopically. At 8 weeks, microscopic changes included a robust inflammatory response around the grafts. All grafts were still intact but in the early stages of degradation. No microtubules, indicative of vas deferens recanalization, were identified. One specimen showed evidence of healing and neovascularization at the interface zone between the vas deferens and the graft. At 12 weeks, grafts were further degraded but still present. Microscopic evaluation showed decreased inflammation. Seven specimens showed neovascularization at the interface zone; two of these showed distinct epithelialized vas deferens microcanals at the graft edges. One specimen showed a microcanal spanning the entire 0.5-cm graft. A time period of 8 weeks is not ample enough for vas deferens regeneration in the setting of a biodegradable PDLA graft; however, early evidence of re-growth was seen at 12 weeks. A longer healing time should permit further biodegradation of the graft, as well as re-growth and possible eventual reconnection of the vas deferens, allowing passage of sperm. These findings suggest a potential role for biodegradable grafts in the reconstruction of vas deferens with long obstructed segments.
Absorbable Implants ; Animals ; Graft Survival ; Male ; Rats ; Rats, Sprague-Dawley ; Vas Deferens ; cytology ; surgery ; Vasectomy ; Vasovasostomy ; methods